Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery.
OBJECTIVE
Cardiac surgery and cardiopulmonary bypass (CPB) induce an inflammatory reaction that may lead to tissue injury. Experimental studies suggest that recombinant human erythropoietin (EPO) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug. This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB.


METHODS
A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital.


METHODS
Patients scheduled for coronary artery bypass graft surgery with CPB.


METHODS
EPO (epoetin alfa, 500 IU/kg intravenously, n = 22) or placebo (n = 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia.


RESULTS
CPB in both groups greatly increased plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-1beta receptor antagonist, IL-6, IL-10, and N-terminal probrain natriuretic peptide (NT-proBNP). Compared with placebo, EPO at day 3 after CPB augmented the TNF-alpha response (p < 0.05) and at 2 hours after CPB increased NT-proBNP (p < 0.05). Also, EPO tended to enhance the CPB-induced increase in IL-1beta receptor antagonist (p = 0.057). Otherwise, EPO had no effect on pro- and antiinflammatory mediators compared with placebo.


CONCLUSIONS
Two large doses of EPO given shortly before CPB do not reduce perioperative release of inflammatory cytokines. In contrast, EPO may augment the TNF-alpha and NT-proBNP response. Although the long-term clinical impact remains unknown, the findings do not support use of EPO as an anti-inflammatory drug in patients undergoing cardiac surgery.
Poulsen
Troels Dirch
TD
Department of Cardiothoracic Anaesthesia, The Heart Centre, Copenhagen University Hospital, Copenhagen, Denmark.
Andersen
Lars Willy
LW
Steinbrüchel
Daniel
D
Gøtze
Jens Peter
JP
Jørgensen
Ole Steen
OS
Olsen
Niels Vidiendal
NV
D000368:Aged; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D004311:Double-Blind Method; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D011300:Preoperative Care / Q000379:methods*; D011446:Prospective Studies; D011994:Recombinant Proteins; D013997:Time Factors
D018836:Inflammation Mediators; D011994:Recombinant Proteins; D004921:Erythropoietin